Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice

Ganesh V. Halade, Md Mizanur Rahman, Arunabh Bhattacharya, Jeffrey L. Barnes, Bysani Chandrasekar, Gabriel Fernandes

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Abstract

The therapeutic efficacy of individual components of fish oils (FOs) in various human inflammatory diseases still remains unresolved, possibly due to low levels of n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or lower ratio of DHA to EPA. Because FO enriched with DHA (FO-DHA) or EPA (FO-EPA) has become available recently, we investigated their efficacy on survival and inflammatory kidney disease in a well-established animal model of human systemic lupus erythematosus. Results show for the first time that FO-DHA dramatically extends both the median (658 d) and maximal (848 d) life span of (NZB x NZW)F1 (B x W) mice. In contrast, FO-EPA fed mice had a median and maximal life span of ∼384 and 500 d, respectively. Investigations into possible survival mechanisms revealed that FO-DHA (versus FO-EPA) lowers serum anti-dsDNA Abs, IgG deposition in kidneys, and proteinuria. Further, FO-DHA lowered LPS-mediated increases in serum IL-18 levels and caspase-1-dependent cleavage of pro-IL-18 to mature IL-18 in kidneys. Moreover, FO-DHA suppressed LPS-mediated PI3K, Akt, and NF-κB activations in kidney. These data indicate that DHA, but not EPA, is the most potent n-3 fatty acid that suppresses glomerulonephritis and extends life span of systemic lupus erythematosus-prone short-lived B 3 W mice, possibly via inhibition of IL-18 induction and IL-18-dependent signaling.

Original languageEnglish (US)
Pages (from-to)5280-5286
Number of pages7
JournalJournal of Immunology
Volume184
Issue number9
DOIs
StatePublished - May 1 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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